Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine
- PMID: 11934675
- DOI: 10.1152/ajpendo.00208.2001
Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine
Abstract
Enhanced protein synthesis in skeletal muscle after ingestion of a balanced meal in postabsorptive rats is mimicked by oral leucine administration. To assess the contribution of insulin to the protein synthetic response to leucine, food-deprived (18 h) male rats (approximately 200 g) were intravenously administered a primed-constant infusion of somatostatin (60 microg + 3 microg.kg(-1).h(-1)) or vehicle beginning 1 h before administration of leucine (1.35 g L-leucine/kg) or saline (control). Rats were killed 15, 30, 45, 60, or 120 min after leucine administration. Compared with controls, serum insulin concentrations were elevated between 15 and 45 min after leucine administration but returned to basal values by 60 min. Somatostatin maintained insulin concentrations at basal levels throughout the time course. Protein synthesis was increased between 30 and 60 min, and this effect was blocked by somatostatin. Enhanced assembly of the mRNA cap-binding complex (composed of eukaryotic initiation factors eIF4E and eIF4G) and hyperphosphorylation of the eIF4E-binding protein 1 (4E-BP1), the 70-kDa ribosomal protein S6 kinase (S6K1), and the ribosomal protein S6 (rp S6) were observed as early as 15 min and persisted for at least 60 min. Somatostatin attenuated the leucine-induced changes in 4E-BP1 and S6K1 phosphorylation and completely blocked the change in rp S6 phosphorylation but had no effect on eIF4G small middle dot eIF4E assembly. Overall, the results suggest that the leucine-induced enhancement of protein synthesis and the phosphorylation states of 4E-BP1 and S6K1 are facilitated by the transient increase in serum insulin. In contrast, assembly of the mRNA cap-binding complex occurs independently of increases in insulin and, by itself, is insufficient to stimulate rates of protein synthesis in skeletal muscle after leucine administration.
Similar articles
-
Orally administered leucine enhances protein synthesis in skeletal muscle of diabetic rats in the absence of increases in 4E-BP1 or S6K1 phosphorylation.Diabetes. 2002 Apr;51(4):928-36. doi: 10.2337/diabetes.51.4.928. Diabetes. 2002. PMID: 11916909
-
Endotoxin disrupts the leucine-signaling pathway involving phosphorylation of mTOR, 4E-BP1, and S6K1 in skeletal muscle.J Cell Physiol. 2005 Apr;203(1):144-55. doi: 10.1002/jcp.20207. J Cell Physiol. 2005. PMID: 15389631
-
Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway.J Nutr. 2000 Oct;130(10):2413-9. doi: 10.1093/jn/130.10.2413. J Nutr. 2000. PMID: 11015466
-
Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine.J Nutr. 2001 Mar;131(3):856S-860S. doi: 10.1093/jn/131.3.856S. J Nutr. 2001. PMID: 11238774 Review.
-
4E-BP1 and S6K1: translational integration sites for nutritional and hormonal information in muscle.Am J Physiol Endocrinol Metab. 2000 Oct;279(4):E715-29. doi: 10.1152/ajpendo.2000.279.4.E715. Am J Physiol Endocrinol Metab. 2000. PMID: 11001751 Review.
Cited by
-
Impacts of protein quantity and distribution on body composition.Front Nutr. 2024 May 3;11:1388986. doi: 10.3389/fnut.2024.1388986. eCollection 2024. Front Nutr. 2024. PMID: 38765819 Free PMC article. Review.
-
Kinetic modeling of leucine-mediated signaling and protein metabolism in human skeletal muscle.iScience. 2023 Dec 5;27(1):108634. doi: 10.1016/j.isci.2023.108634. eCollection 2024 Jan 19. iScience. 2023. PMID: 38188514 Free PMC article.
-
The impact of leucine supplementation on body composition and glucose tolerance following energy restriction: an 8-week RCT in adults at risk of the metabolic syndrome.Eur J Clin Nutr. 2024 Feb;78(2):155-162. doi: 10.1038/s41430-023-01360-1. Epub 2023 Nov 3. Eur J Clin Nutr. 2024. PMID: 37923932 Free PMC article. Clinical Trial.
-
Nutritional Value of Yogurt as a Protein Source: Digestibility/Absorbability and Effects on Skeletal Muscle.Nutrients. 2023 Oct 14;15(20):4366. doi: 10.3390/nu15204366. Nutrients. 2023. PMID: 37892442 Free PMC article. Review.
-
O-GlcNAcylation is a gatekeeper of porcine myogenesis.J Anim Sci. 2022 Nov 1;100(11):skac326. doi: 10.1093/jas/skac326. J Anim Sci. 2022. PMID: 36219104 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous